Accumulation of nano-sized particles in a murine model of angiogenesis |
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Authors: | Thomas R. Wittenborn,Esben K.U. Larsen,Thomas Nielsen,Louise M. Rydtoft,Line Hansen,Jens V. Nygaard,Thomas Vorup-Jensen,Jø rgen Kjems,Michael R. Horsman,Niels Chr. Nielsen |
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Affiliation: | 1. Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark;2. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark;3. Department of Molecular Biology and Genetics, Aarhus University, C.F. Moellers Allé 3, 8000 Aarhus C, Denmark;4. The Lundbeck Foundation Nanomedicine Center for Individualized Management of Tissue Damage and Regeneration (LUNA), Aarhus University, Aarhus, Denmark;5. Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark;6. Department of Engineering, Aarhus University, Finlandsgade 22, 8000 Aarhus, Denmark;g Department of Biomedicine, Aarhus University, Bartholins Allé 6, 8000 Aarhus, Denmark;h Center for Insoluble Protein Structures (inSPIN) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark |
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Abstract: | PurposeTo evaluate the ability of nm-scaled iron oxide particles conjugated with Azure A, a classic histological dye, to accumulate in areas of angiogenesis in a recently developed murine angiogenesis model.Materials and methodsWe characterised the Azure A particles with regard to their hydrodynamic size, zeta potential, and blood circulation half-life. The particles were then investigated by Magnetic Resonance Imaging (MRI) in a recently developed murine angiogenesis model along with reference particles (Ferumoxtran-10) and saline injections.ResultsThe Azure A particles had a mean hydrodynamic diameter of 51.8 ± 43.2 nm, a zeta potential of −17.2 ± 2.8 mV, and a blood circulation half-life of 127.8 ± 74.7 min. Comparison of MR images taken pre- and 24-h post-injection revealed a significant increase in R2* relaxation rates for both Azure A and Ferumoxtran-10 particles. No significant difference was found for the saline injections. The relative increase was calculated for the three groups, and showed a significant difference between the saline group and the Azure A group, and between the saline group and the Ferumoxtran-10 group. However, no significant difference was found between the two particle groups.ConclusionUltrahigh-field MRI revealed localisation of both types of iron oxide particles to areas of neovasculature. However, the Azure A particles did not show any enhanced accumulation relative to Ferumoxtran-10, suggesting the accumulation in both cases to be passive. |
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Keywords: | Angiogenesis Iron oxide particles Ultrahigh-field MRI Sponge model |
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